1. 10/2/2015 AQEEL ALGHAMDI 1

2. PROTEINURIA DR AQEEL ALGHAMDI MBBS,DCH,JBCP,ABP,FBN consultant pediatric nephrology 10/2/20152

3. Contents: Introduction Pathophysiology Causes History Examination Investigations Management

5. Introduction proteinuria on a routine screening urinalysis is common proteinuria on a routine screening urinalysis is common Protein can be found in the urine of healthy children, LESS THAN 150mg/24hr (4 mg/m2/hr) Protein can be found in the urine of healthy children, LESS THAN 150mg/24hr (4 mg/m2/hr)

6. up to 10% of children aged 8-15 yr test positive for proteinuria by urinary dipstick at some time up to 10% of children aged 8-15 yr test positive for proteinuria by urinary dipstick at some time In a 24-hour urine collection: In a 24-hour urine collection: Normal values : <4 mg of protein/m2/hr Normal values : <4 mg of protein/m2/hr Significant values 4–40 mg/m2/hr Significant values 4–40 mg/m2/hr Nephrotic range >40 mg/m2/hr " Nephrotic range >40 mg/m2/hr "

7. The challenge is to differentiate the child with proteinuria related to renal disease from the otherwise healthy child with transient or The challenge is to differentiate the child with proteinuria related to renal disease from the otherwise healthy child with transient or other benign forms of proteinuria other benign forms of proteinuria

8. Causes of proteinuria Isolated Orthostatic Persistant Glomerular tubulointerstitial

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10. 1.Transient Proteinuria The majority of children found to have positive urinary dipstick values for protein have normal dipstick values on repeated measurements The majority of children found to have positive urinary dipstick values for protein have normal dipstick values on repeated measurements

11. The proteinuria usually does not exceed 1-2+ on the dipstick The proteinuria usually does not exceed 1-2+ on the dipstick No evaluation or therapy is needed No evaluation or therapy is needed

12. 2.Orthostatic (Postural) Proteinuria Orthostatic proteinuria is the most common cause of persistent proteinuria in school- aged children and adolescents Orthostatic proteinuria is the most common cause of persistent proteinuria in school- aged children and adolescents Occurring in up to 60% of children with persistent proteinuria Occurring in up to 60% of children with persistent proteinuria

13. Patients with orthostatic proteinuria excrete normal or minimally increased amounts of protein in the supine position. Patients with orthostatic proteinuria excrete normal or minimally increased amounts of protein in the supine position. Children with this condition are usually asymptomatic, and the condition is discovered on routine urinalysis. Children with this condition are usually asymptomatic, and the condition is discovered on routine urinalysis.

14. In the upright position, urinary protein excretion may be increased 10-fold, up to 1,000 mg/24 hr (1 g/24 hr). In the upright position, urinary protein excretion may be increased 10-fold, up to 1,000 mg/24 hr (1 g/24 hr).

15. 3.Persistant Proteinuria proteinuria indicates renal disease proteinuria indicates renal disease and may be caused by either : and may be caused by either : glomerular or tubular disorders glomerular or tubular disorders Significant proteinuria on a first morning urine sample on 3 consecutive days (>1+ on dipstick,urine specific gravity >1.015 or protein : creatinine ratio >0.2) Significant proteinuria on a first morning urine sample on 3 consecutive days (>1+ on dipstick,urine specific gravity >1.015 or protein : creatinine ratio >0.2)

16. Initial evaluation of a child with persistant Initial evaluation of a child with persistant proteinuria should include : proteinuria should include : - Measurement of serum creatinine - Measurement of serum creatinine and electrolyte and electrolyte - First morning urine protein :creatinine - First morning urine protein :creatinine ratio ratio - Serum albumin level - Serum albumin level - Complement levels. - Complement levels.

17. I. Glomerular Proteinuria Glomerular proteinuria can range from <1 g to Glomerular proteinuria can range from <1 g to >30 g/24 hr. >30 g/24 hr. Glomerular proteinuria results from alterations in the permeability of any of the layers of the glomerular capillary wall to normally filtered proteins and occurs in a variety of renal diseases. " Glomerular proteinuria results from alterations in the permeability of any of the layers of the glomerular capillary wall to normally filtered proteins and occurs in a variety of renal diseases. "

18. Glomerular proteinuria should be suspected Glomerular proteinuria should be suspected in any patient with: in any patient with: - First morning urine protein : creatinine - First morning urine protein : creatinine ratio >1.0, or ratio >1.0, or - Proteinuria accompanied by: - Proteinuria accompanied by:. Hypertension. Hypertension. Hematuria. Hematuria. Edema. Edema. Renal dysfunction. Renal dysfunction

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20. ii. Tubular Proteinuria A variety of renal disorders that primarily involve the tubulointerstitial compartment of the kidney can cause low-grade fixed proteinuria (protein : creatinine ratio <1.0 A variety of renal disorders that primarily involve the tubulointerstitial compartment of the kidney can cause low-grade fixed proteinuria (protein : creatinine ratio <1.0

21. Injury to the proximal tubules can result in: Injury to the proximal tubules can result in: Diminished reabsorptive capacity Diminished reabsorptive capacity Loss of these low molecular weight proteins Loss of these low molecular weight proteins in the urine in the urine Tubular proteinuria may be seen in acquired and inherited disorders and may be associated with other defects of proximal tubular function, such as the Fanconi syndrome. the Fanconi syndrome. (glycosuria, phosphaturia, bicarbonate (glycosuria, phosphaturia, bicarbonate wasting, and aminoaciduria). wasting, and aminoaciduria).

22. Asymptomatic persistent proteinuria glomerular rather than tubular proteinuria Asymptomatic patients having persistent proteinuria generally have glomerular rather than tubular proteinuria X-linked tubular syndromeDent disease Tubular proteinuria is a consistent finding among patients with the X-linked tubular syndrome, Dent disease, caused by mutations of the renal chloride channel

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24. In occult cases, glomerular and tubular proteinuria can be distinguished by electrophoresis of the urine. In occult cases, glomerular and tubular proteinuria can be distinguished by electrophoresis of the urine. In tubular proteinuria, little or no albumin is detected, whereas in glomerular proteinuria the major protein is albumin In tubular proteinuria, little or no albumin is detected, whereas in glomerular proteinuria the major protein is albumin.

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34. Asymptomatic proteinuria 1 Hematuria or other signs of kidney disease Nonrenal diseases Recheck when resolves Isolated proteinuria Collected 12 –hr Recumbent urine < 50 mg/m2/12hr I solated intermittent Proteinuria or orthostatic proteinuria Reassure 90% No Yes

35. Asymptomatic proteinuria 2 Hematuria or other signs of kidney disease Nonrenal diseases Isolated proteinuria Collected 12 –hr Recumbent urine 50 - 200mg/m2/12hr Limited evaluation BUN,Creatinine,S.electrolytes Spot UPr: UCr ratio, S.Total protein C3,C4,ASOT, Lupus serology (selected cases) Renal imaging,index of tubular proteinuria Follow -up 5% No Normal

36. Asymptomatic proteinuria 3 Hematuria or other signs of kidney disease Nonrenal diseases Isolated proteinuria Collected 12 –hr Recumbent urine >200mg/m2/12hr 50 - 200mg/m2/12hr Limited evaluation BUN,Creatinine,S.electrolytes Spot UPr: UCr ratio, S.Total protein C3,C4,ASOT, Lupus serology (selected cases) Renal imaging,index of tubular proteinuria Evaluation Consider referral S.Total protein HIV status Fractionated 24-hr urine collection S. Albumin S. Cholesterol ASOT C3,C4 ANA, anti-DNA GFR Renal imaging Renal biopsy Abnormal Yes 5% No